Isobutylene → HCID 59149704, compound

HRID 1675071Notes

Reaction equation

HRID 1675071 reaction equation
O1C[CH2:5][CH:4]([O:7][CH2:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:16]=[CH:17][C:18]4[N:19]([C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][N:23]=4)[N:20]=3)[CH2:11][CH2:10]2)[CH2:3]C1.O.[C:29]1(C)C=CC(S(O)(=O)=O)=CC=1.CC(C)=C>C(Cl)Cl>[C:4]([O:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:19]([C:21]([C:24]([F:27])([F:25])[F:26])=[N:22][N:23]=3)[N:20]=2)[CH2:13][CH2:14]1)([CH3:5])([CH3:29])[CH3:3]

Participants

5

Reactant 3

HCID 8255IsobutyleneHCID 521998p-Toluenesulfonic acid monohydrateHCID 59149778HCID 59149778, compound

Product 1

HCID 59149704HCID 59149704, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirred solution of [1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]methanol (obtained as described in Example 294, preparation of starting materials) (151 mg, 0.5 mmol) and p-toluenesulfonic acid monohydrate (190 mg, 1.0 mmol) in DCM (2 mL) was cooled to −70° C. and 2-methylpropene (1 mL, 10.48 mmol) was condensed in from a cylinder. The mixture was stirred for 2 days at ambient temperature in a sealed tube. The tube was re-cooled to open then allowed to warm to ambient temperature with stirring. The solution was diluted with DCM and washed with 2M aqueous K2CO3. The organic phase was dried over MgSO4 and evaporated. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-(4-(tert-butoxymethyl)piperidin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (98 mg, 54%) as a white solid.

Workup

  1. customcondensed in from a cylinder
  2. temperatureThe tube was re-cooled
  3. temperatureto warm to ambient temperature
  4. stirringwith stirring
  5. washwashed with 2M aqueous K2CO3
  6. dry with materialThe organic phase was dried over MgSO4
  7. customevaporated
  8. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-ff2d597d012f47c78f292f3a3744224e
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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